ArticleProceedings of the National Academy of Sciences of the United States of America2016
Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
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- Phosphatase-independent activity of smooth-muscle calcineurin orchestrates a gene expression program leading to hypertension.PLoS biology · 2025Article
- Preventive and Therapeutic Effects of Sericin-Derived Oligopeptides (SDOs) from Yellow Silk Cocoons on Blood Pressure Lowering in L-NAME-Induced Hypertensive Rats.Foods (Basel, Switzerland) · 2025Article
- Cellular Senescence Genes as Cutting-Edge Signatures for Abdominal Aortic Aneurysm Diagnosis: Potential for Innovative Therapeutic Interventions.Journal of cellular and molecular medicine · 2025Article
- Mitochondrial Ca2+-coupled generation of reactive oxygen species, peroxynitrite formation, and endothelial dysfunction in Cantú syndrome.JCI insight · 2024Article
- Hyperoside ameliorates cerebral ischaemic-reperfusion injury by opening the TRPV4 channelPharmaceutical biology · 2023Article
- Cracking the Endothelial Calcium (CaInternational journal of molecular sciences · 2023Review
- Re: Differential benefits of physical training associated or not with L-Arginine supplementation in rats with metabolic syndrome: Evaluation of cardiovascular, autonomic and metabolic parameters.Physiology & behavior · 2023Article
- Newly synthesized glycoprotein profiling to identify molecular signatures of warm ischemic injury in donor lungs.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Experimental evidence and clinical implications of Warburg effect in the skeletal muscle of Fabry disease.iScience · 2023Article
- Zhijing powder manages blood pressure by regulating PI3K/AKT signal pathway in hypertensive rats.Heliyon · 2023Article
- SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.Cellular and molecular life sciences : CMLS · 2022Article
- Endothelial Retargeting of AAV9 In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- IP3 receptor orchestrates maladaptive vascular responses in heart failure.The Journal of clinical investigation · 2022Article
- Targeting the ASMase/S1P pathway protects from sortilin-evoked vascular damage in hypertension.The Journal of clinical investigation · 2022Article
- Association Between Circulating Regulator of Calcineurin 2 Concentrations With Overweight and Obesity.Frontiers in endocrinology · 2022Article
- Aberrant CaScience signaling · 2021Article
- Glypican 1 and syndecan 1 differently regulate noradrenergic hypertension development: Focus on IP3R and calcium.Pharmacological research · 2021Article
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Endothelial cells (ECs) are critical mediators of blood pressure (BP) regulation, primarily via the generation and release of vasorelaxants, including nitric oxide (NO). NO is produced in ECs by endothelial NO synthase (eNOS), which is activated by both calcium (Ca(2+))-dependent and independent pathways. Here, we report that intracellular Ca(2+) release from the endoplasmic reticulum (ER) via inositol 1,4,5-trisphosphate receptor (IP3R) is required for Ca(2+)-dependent eNOS activation. EC-specific type 1 1,4,5-trisphosphate receptor knockout (IP3R1(-/-)) mice are hypertensive and display blunted vasodilation in response to acetylcholine (ACh). Moreover, eNOS activity is reduced in both isolated IP3R1-deficient murine ECs and human ECs following IP3R1 knockdown. IP3R1 is upstream of calcineurin, a Ca(2+)/calmodulin-activated serine/threonine protein phosphatase. We show here that the calcineurin/nuclear factor of activated T cells (NFAT) pathway is less active and eNOS levels are decreased in IP3R1-deficient ECs. Furthermore, the calcineurin inhibitor cyclosporin A, whose use has been associated with the development of hypertension, reduces eNOS activity and vasodilation following ACh stimulation. Our results demonstrate that IP3R1 plays a crucial role in the EC-mediated vasorelaxation and the maintenance of normal BP.
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